Marley wrote the song while touring Haiti, deeply moved by its poverty and the lives of Haitians, according to his then-girlfriend Esther Anderson. The song was frequently performed at Marley's concerts, often as the last song. "Get Up, Stand Up" was also the last song Marley ever performed on stage, on 23 September 1980 at the Stanley Theater, now the Benedum Center in Pittsburgh, Pennsylvania.
On his DVD Live at the Hollywood Bowl, artist Ben Harper relates a childhood experience in which, during a 1978 Bob Marley concert at the Starlight Amphitheater, Peter Tosh showed up unannounced as this song was being performed, took the microphone from Marley and started singing the last verse of the song to thunderous applause. Tosh was on tour opening for the Rolling Stones at the time.
The song was re-recorded and re-released by the three major Wailers on their own solo releases, each with varying arrangements and approaches to the third verse, which claims that "Almighty God is a living man". Bob Marley and the Wailers released a Bob Marley only version on Live! in 1975, this version was notable for the "WO-YO!" refrain after the third verse. Tosh would include his own solo version on his second album, Equal Rights in 1977. Bunny Wailer was the last to release his own version on Protest. This version actually featured Tosh due to his involvement in recording the album before his death.
The song was parodied on an episode of the television series Futurama, entitled "The Route of All Evil". In the episode, Jamaican accountant Hermes Conrad alters the lyrics of the song by singing "Stamp it, file it, send it over night."
The song is found on Toots & the Maytals' LP Pass the Pipe. Although sung with completely different lyrics and melody, the songwriting credit is given to the Wailers.